Ovarian cancer is second only to breast cancer as the most common cause of death from gynecological malignancy in women in this country. The principal objective of this project is to identify antigens or markers of ovarian tumors which can be used in an immunodiagnostic assay for the detection of early ovarian cancer. Xenogeneic sera will be used to identify (l) antigens in extracts of ovarian tumors and (2) cell surface and shed antigens of cultured ovarian tumor cell lines. Using rabbit antisera we have already identified two antigens (OvC-l and OvC-2) present in ovarian tumors but not in normal ovaries. Both these antigens are present in amniotic fluid and this is a convenient source of material for isolation of the antigens. OvC-l is a new pregnancy-associated antigen; two forms have been identified in extracts of ovarian tumors: (1) a glycoprotein of 48,000d and (2) a protein of 20,000d. The former has been isolated and purified from amniotic fluid. OvC-2 is a new onco-fetal antigen and is found in fetal intestine as well as ovarian tumors. It is a protein of 64,000d having some properties in common with albumin. The development of sensitive assays (e.g. radioimmunoassays) capable of detecting these antigens in sera or plasma will enable us to determine their possible usefulness for the immunodiagnosis of ovarian cancer. We have recently developed a new procedure for establishing long term ovarian tumor cell lines. These cultured cells will be used in attempts to identify new antigens not previously identified using tumor extracts. Components shed from cultured ovarian tumor cells will be studied will the idea that these antigens may be analogous to those released into the blood by tumors in vivo. Antisera to the cultured cells and their released components will be raised in rabbits and monoclonal antibodies will be produced using the procedure of Kohler and Milstein. The specificity of the antisera will be studied by serological techniques using binding or adherence assays and by radioimmunoprecipitation. New antigens showing ovarian tumor specificity will be examined for their possible use in the early detection of ovarian cancer.